US2439749A - Nu-alkyl thiamorpholines and derivatives - Google Patents

Description

Patented Apr. 13, 1948 N-ALKYL THIAMOBPHOLINES AND DERIVATIVES Joseph B. Niederl, Brooklyn, N. Y., and William F. Hart, Easton, Pa.

No Drawing. Application May 3, 1945, Serial No. 591,850

4 Claims. (01. 260-243) 1 2 This invention relates to the utilization of a N-alkyl-thiamorpholine-l-oxides: war gas, di-(fi-chloro-ethyl) sulfide (mustard 2HCl as), and its oxidation products in the manu- (0103103989 "'f PNwmcmhso facture of useful products, such products finding 'N'alkyl-thlamorphohhe-l-dloxldes1 application as anti-oxidants, as detergents, wet- ENE (CICHZCHQSOZ IPMCHZCHMSO ting and flotation agents, as well as bactericides, The tertiary amine Salts [zwHzcHznNmHx] fungicides and antiseptics.

of the foregoing compounds are prepared by More partlculafly thls Invention relates to the treating the free bases with mineral or with or preparation from mustard gas of N-alkyl thimor- I ganic acids, while the quaternary ammonium $31 3 5; l l i o ifgt l fid o i fiafil yffih faggfi salts [ZtCHzCHz)2NR(R/)Xl are prepared by the pholine oxides and dioxides in which the alkyl Interact)? the m f bases 3 alkyl radical contains the same number of carbon gi g ifgffgs fiit g figi b zi gg esters atoms, and which are prepared from the oxidation products of mustard gas, di-(p-chloro-ethyl) xample 1.N-cetyl ihwmorpholme sulfoxide and di-(B-chloro-ethyl) sulfone. seventy-six grams of cetyl amine (B. P. 325

This invention also relates to the derivatives of meow are dissolved in 120 of absolute 1- such long chain substituted thiamorpholines, 601101 and 34 of anhydrous Sodium carbonate thiamorpholine-oxides and. thiamorpholine-diaddedgrams of mustard gas are then Oxides in Which the nitrogen atom may not only added, and the solution refluxed for eight hours. be trivalent but a so pentwvalent. Such The warm solution is filtered to remove inorpounds having proven to be surface active agents. m salts, which are washed twice with hot The Various types of compounds Involved in thls absolute alcohol. The combined alcohol extracts inv may be eXpressed by the followmg are distilled in vacuo to remove the solvent. The eral formula: residue is then taken up in an excess of dry ether, onion, and saturated with dry hydrogen chloride. The

hydrochloride is filtered ofl and washed repeat- \CH2C/h edly with d y ether and with acetone. The free base is obtained by taking up the hydrochloride In the above general f a. Z r pr $111- in a concentrated potassium hydroxide solution a dB, or a sulfone group. While Y and extracting Withether. The combined ether represents: extracts are dried over solid potassium hydroxide pellets, and the solvent removed by distillation. or NR(R )X The free base is purified by recrystallization from N being nitrogen, R a long chain alkyl radical of acetone from 12 to 18 car on atoms, a Short Cham Substitution in the above procedure of the cetyl alkyl a yl rad cal, and X an an o amine by appropriate amounts of other long In preparing the compounds enumerated ahove, chain primary amines, such as dodecyl-, tridecyb, mustard gas, or its Oxi atio P t l tetradecyl-, peta'decyl-, hept-adecyior octadecyl c o yl) sulfoxide or slllfonel, 1S reactefi 40 amines, produces the respective N-alkyl thiamorwith l chain P y amlhes (dodecyl'w pholines, the physical and chemical properties of q w i e penta-decyh, hexa'decyl" some of which are summarized below. hepta-decy1-, or octa-decylamine) to yield the respective long chain substituted N-alkyl thia- M P 00 C MRHYdm morpholine, N-alkyl thiamorphohne-oxide and chloride N-alkyl thiamorpholine-dioxide in accordance Win i n 2 N-Dodecyl-thiamor h l' 159 wlth the 0110 g equat o s lg-getraiecyll-tigillam orgfii gllgne 15;

-31]; exa ecyamorp ome 162 N yl thiamorphonnes' H01 N-Octadecyl-thiamorplioline 131 173 --2 ENE: +(c1cmcrms rpmcmcmns 0 Example 2.--N-cetyZ-thiamorphoZine-I-o:cide

Fifty-five grams of cetyl amine (B. P. 325 C. (uncor.) and forty grams of di-(s-chloro-ethyl) sulfoxide (M. P. 109) are dissolved in 500 cc. of 95% alcohol and 24.1 grams of powdered anhydrous sodium carbonate are added. The reaction mixture is refluxed for three hours and the hot solution is filtered to remove inorganic salts, washing twice with hot alcohol. The product crystallizes in quite pure form, which may be further purified by a re-crystallization from alcohol.

The hydrochloride is prepared by dissolving the product in dry benzene and passing in dry hydrogen chloride gas, and purified by re-crystallization from benzene or alcohol, and finally washing with dry acetone.

Substitution in the above procedure of the cetyl amine by appropriate amounts of other long chain substituted primary amines produces the respective N-alkyl-thiamorpholine-l-oxides, the physical and chemical properties of some of which are summarized below.

Example 3.N-cetyZ-thiamorpholine-Idioxide Fifty and five-tenths grams of cetyl amine (B. P. 325 C. (uncor) and forty grams of di-(s-chloro-ethyl) sulfone are dissolved in 500 cc. of alcohol, and 22.2 grams of powdered anhydrous sodium carbonate is added. This reaction mixture is refluxed for one hour, the warm solution filtered to remove inorganic salts, and the salts washed twice with hot alcohol. The product crystallizes on cooling and may be further purified by one re-crystallization from alcohol. The hydrochloride is prepared by dissolving the product in dry benzene and passing in dry hydrogen chloride gas. This may be further purified by recrystallization from benzene or alcohol, finally washing with dry acetone.

Again, substitution in the above procedure of the cetyl amine by appropriate amounts of other long chain primary amines produces the respective N-alkyl-thiamorpholine-l-dioxides, the physical and chemical properties of some of which are tabulated below:

M. P. Hydro- M. P. 0 C. chloride N-Dodecyl thiamorpholine-l-dioxide 73 173 N -Tetradecyl-thiamorpholine-ldioxide 85 169 N-Hexadecyl-thiamorpholine-lo e 88 160 N-Octadecyl-thiamorpholine-ldioxide 92 151 Example 4.Quatemary ammonium alkyl sulfates stroy any unreacted di-alkyl sulfate, and a little decolorizing carbon. The solution is than filtered, and the methanol removed by vacuum distillation. The product is taken up in the least quantity of warm water. The products are usually crystallized irom concentrated water solution and are washed with dry acetone alter filtering and air drying.

These quaternary ammonium sulfates are soluble in water; the ethosulfates are usually about two times soluble in water as the respective metho-sulfates. The physical properties 01 some of these capillary active substances are enumerated below.

M. P. C. N-cetyl-N-methyl-thiamorpholinium methosulfate 210 N -cetyl N-methyl-thiamorpholinium-l -oxide methosulfate 222 N-cetyl-N-methyl-thiamorpholinium-l-dioxide methosulfate N -oetyl-N-ethyl-thiamorpholinium ethosulfate 202 N-cetyl N-ethyl-thiamorpholinium- -oxide ethosulfate 215 N -cetyl-N-ethyl-thiamorpholinium-l-dioxide ethosulfate 173 Example 5 .--Quatemary ammonium halides The methiodides and ethiodides are prepared by refluxing for three hours the respective N-alkyl-thiamorpholines, N-alkyl-thiamorpholine-l-oxides, or N-alkyl-thiamorpholine-l-dioxides with a slight excess of methyl or ethyl iodide, respectively. After refluxing, the excess alky iodide is allowed to evaporate or is removed by distillation under diminished pressure. The residue is usually crystallized from hot ethyl acetate.

Refluxing of the above free bases with molar quantities of benzyl chloride, or an alkyl bromide in toluene solution for six hours, produces the corresponding quaternary ammonium chlorides or bromides, respectively. The solvent is usually removed by distillation in vacuo, the residue is then washed with dry acetone and finally also crystallized from hot ethyl acetate.

Some or the quaternary ammonium halides produced by the above procedure are given below.

M. P. C. N cetyl N methyl thiamorpholinium iodide 224 N-cetyl-N-methyl-thiamorpholinium-l-oxide iodide 234 N-cetyl-N-methyl thiamorpholinium-1-dioxide iodide N-cetyl-N-ethyl-thiamorpholinium iodide 205 N-cetyl N benzyl-thiamorpholinium chloride 166 N-cetyl-N-n-propyl thiamorpholinium bromide 225 N cetyl N benzyl-thiamorpholinium bromide 198 Example 6.Double quaternary ammonium salts in which Z represents an atomic grouping selected from the class consisting of S, 80, and 802, R an alkyl radical containing from 12 to 18 carbon'atoms, R a short chain alkyl radical. x an anion.

2. Compounds of the general formula:

cmcm n in which It represents an alkyl radical containing from 12 to 18 carbon atoms and R a short chain alkyl radical.

3, Compounds of the general formula:

onion, 3 OS\ 3 cmcfi. sum

6 in which It represents an alkyl radical containing from 12 to 18 carbon atoms and R a short chain alkyl radical.

4. Compounds of the general formula:

CHICK! R O S\ (R' CHaCr 504K.

in which R represents an alkyl radical contain- 7 ing from 12 to 18 carbon atoms and R a short chain alkyl radical.

JOSEPH B. NIEDERL. WILLIAM F. HART.

REFERENCES CITED The following references are of record in the flle of this patent:

UNITED STATES PATENTS 20 Number Name Date 2,001,584 Reed May 14, 1935 2,129,805 Wilson Sept. 18, 1988 2,295,504 Shelton Sept. 8, 1942- FOREIGN PATENTS Number Country Date 133,108 Great Britain Sept. 26, 1919 OTHER REFERENCES Journal of the American Chemical Society, vol.

66, pages 840-1.

Chemical Reviews, vol. 15 (1934), pages 452-460. Journal of the American Chemical Society, vol. 47 (1925). Pp. 2821-2831.